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Recent studies have demonstrated that wild-type APP can protect against p53 mediated apoptosis, whereas FAD mutant APP (FADAPP) cannot. N3 rat neuroblastoma cells which are deficient in APP were transfected with wtAPP or FADAPP and then irradiated with UV light to induce apoptosis. In this paradigm inhibition of Aβ restores the anti-apoptotic function of FADAPP, leading Li Gan (122.5) to conclude that the balance between APP and Aβ is critical in determining whether or not a cell will proceed down the cell death pathway. Interestingly, extracellular Aβ did not have a significant effect indicating that intracellular Aβ is the "bad guy" and that it either activates p53 or causes it's nuclear translocation, whereas APP prevents p53 activation.—Dominic Walsh